Yingmei Liu

High Prevalence of Macrolide Resistance in Mycoplasma pneumoniae Isolates from Adult and Adolescent Patients with Respiratory Tract Infection in China

The resistance rate of 67 Mycoplasma pneumoniae isolates from 356 ambulatory adult patients with respiratory tract infection was 69% (46 of 67). All 46 macrolide-resistant strains harbored point mutations in the 23S ribosomal RNA gene. Patients infected with macrolide-resistant M. pneumoniae required significantly longer durations of antibiotic therapy and had longer time to resolution of fever.

Characterization of Community Acquired Staphylococcus aureus Associated with Skin and Soft Tissue Infection in Beijing: High Prevalence of PVL+ ST398

Adult community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) and methicillin-susceptible S aureus (CA-MSSA) skin and soft tissue infection (SSTI) in China is not well described. A prospective cohort of adults with SSTI was established between January 2009 and August 2010 at 4 hospitals in Beijing. Susceptibility testing and molecular typing, including multilocus sequence typing, spa, agr typing, and toxin detection were assessed for all S. aureus isolates. Overall, 501 SSTI patients were enrolled. Cutaneous abscess (40.7%) was the most common infection, followed by impetigo (6.8%) and cellulitis (4.8%). S. aureus accounted for 32.7% (164/501) of SSTIs. Five isolates (5/164, 3.0%) were CA-MRSA. The most dominant ST in CA-MSSA was ST398 (17.6%). The prevalence of Panton-Valentine Leukocidin (pvl) gene was 41.5% (66/159) in MSSA. Female, younger patients and infections requiring incision or drainage were more commonly associated with pvl-positive S. aureus (P<0.03); sec gene was more often identified in CC5 (P<0.03); seh gene was more prevalent in CC1 (P = 0.001). Importantly, ST59 isolates showed more resistance to erythromycin, clindamycin and tetracycline, and needed more surgical intervention. In conclusion, CA-MRSA infections were rare among adult SSTI patients in Beijing. Six major MSSA clones were identified and associated with unique antimicrobial susceptibility, toxin profiles, and agr types. A high prevalence of livestock ST398 clone (17.1% of all S. aureus infections) was found with no apparent association to animal contact.

Molecular characteristics of carbapenemase-producing Enterobacteriaceae in China from 2008 to 2011: Predominance of KPC-2 enzyme

Among 228 carbapenem-nonsusceptible Enterobacteriaceae isolated in China, 65 were carbapenemase-producing Enterobacteriaceae (CPE). Among them, 41, 22, 1, and 1 produced KPC-2, IMP-4, IMP-8, and IMP-1, respectively. KPC-2-producing CPE showed higher resistance than IMP-4-producing ones. Furthermore, the first outbreak of ST11 KPC-2-producing Klebsiella pneumoniae in a Beijing second-degree hospital was identified.

Linezolid-resistant clinical isolates of enterococci and Staphylococcus cohnii from a multicentre study in China: molecular epidemiology and resistance mechanisms

Genetic characterisation of linezolid-resistant Gram-positive cocci in a multicentre study in China has not been reported previously. To study the mechanism underlying the resistance of linezolid-resistant isolates, nine Enterococcus faecalis, one Enterococcus faecium and three Staphylococcus cohnii isolates with various levels of resistance were collected from five hospitals across China in 2009-2012. The nine E. faecalis isolates were classified into seven sequence types, indicating that these linezolid-resistant E. faecalis isolates were polyclonal. Enterococci isolates had reduced susceptibility to linezolid (MICs of 4-8 mg/L) and had mutation of ribosomal protein L3, with three also having mutation of L4, but without the multidrug resistance gene cfr or the 23S rRNA mutation G2576T. The three S. cohnii isolates were highly resistant to linezolid (MICs of 64 mg/L to >256 mg/L), harboured the cfr gene and had the 23S rRNA mutation G2576T. Southern blotting indicated that the cfr gene of these three isolates resided on different plasmids (pHK01, pRM01 and pRA01). In plasmid pHK01, IS21-558 and the cfr gene were integrated into transposon Tn558. In plasmids pRM01 and pRA01, the cfr gene was flanked by two copies of an IS256-like insertion sequence, indicating that the transferable form of linezolid resistance is conferred by the cfr gene. In conclusion, the emergence of linezolid-resistant Gram-positive cocci in different regions of China is of concern. The cfr gene and the 23S rRNA mutation contribute to high-level linezolid resistance in S. cohnii, and the L3 and L4 mutations are associated with low-level linezolid resistance in enterococci.

Neuraminidase inhibitors, superinfection and corticosteroids affect survival of influenza patients

We aimed to study factors influencing outcomes of adults hospitalised for seasonal and pandemic influenza. Individual-patient data from three Asian cohorts (Hong Kong, Singapore and Beijing; N=2649) were analysed. Adults hospitalised for laboratory-confirmed influenza (prospectively diagnosed) during 2008–2011 were studied. The primary outcome measure was 30-day survival. Multivariate Cox regression models (time-fixed and time-dependent) were used. Patients had high morbidity (respiratory/nonrespiratory complications in 68.4%, respiratory failure in 48.6%, pneumonia in 40.8% and bacterial superinfections in 10.8%) and mortality (5.9% at 30 days and 6.9% at 60 days). 75.2% received neuraminidase inhibitors (NAI) (73.8% received oseltamivir and 1.4% received peramivir/zanamivir; 44.5% of patients received NAI ≤2 days and 65.5% ≤5 days after onset of illness); 23.1% received systemic corticosteroids. There were fewer deaths among NAI-treated patients (5.3% versus 7.6%; p=0.032). NAI treatment was independently associated with survival (adjusted hazard ratio (HR) 0.28, 95% CI 0.19–0.43), adjusted for treatment-propensity score and patient characteristics. Superinfections increased (adjusted HR 2.18, 95% CI 1.52–3.11) and chronic statin use decreased (adjusted HR 0.44, 95% CI 0.23–0.84) death risks. Best survival was shown when treatment started within ≤2 days (adjusted HR 0.20, 95% CI 0.12–0.32), but there was benefit with treatment within 3–5 days (adjusted HR 0.35, 95% CI 0.21–0.58). Time-dependent analysis showed consistent results of NAI treatment (adjusted HR 0.39, 95% CI 0.27–0.57). Corticosteroids increased superinfection (9.7% versus 2.7%) and deaths when controlled for indications (adjusted HR 1.73, 95% CI 1.14–2.62). Early NAI treatment was associated with shorter length of stay in a subanalysis. NAI treatment may improve survival of hospitalised influenza patients; benefit is greatest from, but not limited to, treatment started within 2 days of illness. Superinfections and corticosteroids increase mortality. Antiviral and non-antiviral management strategies should be considered. NAI treatment, secondary infections and corticosteroids may impact on survival of hospitalised influenza patients http://ow.ly/ErOsT

Viral and Mycoplasma pneumoniae community-acquired pneumonia and novel clinical outcome evaluation in ambulatory adult patients in China.

Few studies have addressed the etiology and clinical outcomes of community-acquired pneumonia (CAP) treated in an ambulatory setting. We investigated the etiology by the culture of Mycoplasma pneumoniae, urine antigen testing of Streptococcus pneumoniae and Legionella pneumoniae, and DNA or RNA determination of eight kinds of respiratory virus DNA or RNA. An etiological diagnosis was made in 51.8% of 197 patients. The most common pathogens were M. pneumoniae (29.4%) followed by influenza virus A, parainfluenza virus, adenovirus, human metapneumovirus (9.6%), and S. pneumoniae (4.1%). Patients with mycoplasma infections were younger, less likely to have comorbidities, and less likely to have adequate sputum for gram stain and culture. Patients with viral infections were older and more likely to have poorly defined nodules on chest X-ray (CXR) or computed tomography (CT) scan. Among patients infected with M. pneumoniae, those with quinolones as initial prescriptions had shorter duration of fever after the initiation of antibiotics than patients with β-lactams, macrolides, or β-lactams + macrolides (p < 0.05). This study suggests that M. pneumoniae and respiratory viruses were the most frequent pathogens found in ambulatory adult CAP patients and quinolones were better than β-lactams, macrolides, or β-lactams + macrolides in the resolution of fever of M. pneumoniae pneumonia.

Clinical Features of Pneumonia Caused by 2009 Influenza A(H1N1) Virus in Beijing, China

Background Data on symptoms and radiographic changes in patients with pandemic 2009 influenza A(H1N1) (A[H1N1]) pneumonia during convalescence have not been reported. Methods During October 26, 2009, and January 23, 2010, adult patients with pneumonia with laboratory-confirmed or clinically suspected A(H1N1) infections were observed for clinical characteristics, high-resolution chest CT scan, and lung function test changes during acute and 3-month convalescent phases. Results Of the 65 case subjects, the median age was 41 (interquartile range [IQR], 28-57) years, 60.0% were men, and 55.4% had at least one underlying medical condition. Sixty-two patients started oseltamivir therapy within a median of 5 (IQR, 4-6) days from the onset of illness, and 31 received IV corticosteroids. ARDS developed in 33 patients, and 24 were treated initially with noninvasive positive pressure ventilation (NPPV). In this group, NPPV was successful in 13 patients (54.2%). Nine patients died at a median of 16 (IQR, 10-24) days after onset of illness. Multivariate Cox regression identified two independent risk factors for death: progressive dyspnea after resolution of fever (relative risk, 5.852; 95% CI, 1.395-24.541; P = .016) and a higher APACHE (Acute Physiology and Chronic Health Evaluation) II score on presentation (relative risk for each point, 1.312; 95% CI, 1.140-1.511; P < .001). At 3-month follow-up of survivors with A(H1N1), ground-glass opacities were still present, although diminished, in 85.7%, and diffusing capacity for carbon monoxide was mildly reduced in 61.5%. Conclusions Ground-glass opacities and decreased diffusing capacity were the main abnormalities observed at 3-month follow-up of survivors of A(H1N1).

A NEW TN1546 TYPE OF VANB PHENOTYPE-VANA GENOTYPE VANCOMYCIN-RESISTANT ENTEROCOCCUS FAECIUM ISOLATES IN MAINLAND CHINA

VanB phenotype-vanA genotype vancomycin-resistant Enterococcus faecium (VREF) has never been reported in mainland China. We investigated the frequency and molecular characteristics of this strain in a Beijing tertiary hospital. Of 23 vanA genotype VREF clinical isolates, 12 (54.3%) were VanB phenotype-vanA genotype. Mutilocus sequence typing (MLST) analysis revealed that all isolates belong to a single clonal complex (CC78), which has been disseminated worldwide. Based on MLST and pulsed-field gel electrophoresis, 23 isolates were polyclonal dissemination in our hospital. Tn1546-like element structure analysis showed that of 12 VanB phenotype-vanA genotype isolates, 5 had complete deletion of vanY and vanZ accompanying insertion of IS1216V in vanX-vanY intergenic region, 5 had ISEfa4 insertion in orf2-vanR intergenic region, a new Tn1546 structure type, and 2 were identical to VanA phenotype-vanA genotype VREF. Data showed that the deletion of vanY and vanZ genes or ISEfa4 insertion in orf2-vanR intergenic region can partly explain the causes of difference between phenotype and genotype.

Specific Multilocus Variable-Number Tandem-Repeat Analysis Genotypes of Mycoplasma pneumoniae Are Associated with Diseases Severity and Macrolide Susceptibility

Clinical relevance of multilocus variable-number tandem-repeat (VNTR) analysis (MLVA) in patients with community-acquired pneumonia (CAP) by Mycoplasma pneumoniae (M. pneumoniae) is unknown. A multi-center, prospective study was conducted from November 2010 to April 2012. Nine hundred and fifty-four CAP patients were consecutively enrolled. M. pneumoniae clinical isolates were obtained from throat swabs. MLVA typing was applied to all isolates. Comparison of pneumonia severity index (PSI) and clinical features among patients infected with different MLVA types of M. pneumoniae were conducted. One hundred and thirty-six patients were positive with M. pneumoniae culture. The clinical isolates were clustered into 18 MLVA types. One hundred and fourteen (88.3%) isolates were resistant to macrolide, covering major MLVA types. The macrolide non-resistant rate of M. pneumoniae isolates with Mpn13-14-15-16 profile of 3-5-6-2 was significantly higher than that of other types (p≤0.001). Patients infected with types U (5-4-5-7-2) and J (3-4-5-7-2) had significantly higher PSI scores (p<0.001) and longer total duration of cough (p = 0.011). Therefore it seems that there is a correlation between certain MLVA types and clinical severity of disease and the presence of macrolide resistance.

Viral etiology of community-acquired pneumonia among adolescents and adults with mild or moderate severity and its relation to age and severity

BackgroundBetter knowledge of distribution of respiratory viruses (RVs) in adolescents and adults with community-acquired pneumonia (CAP) is needed.MethodsTo investigate the RVs etiology among adolescents and adults with CAP, according to age and pneumonia severity index (PSI), a multi-center, prospective study was conducted from November 2010 to April 2012. Fifteen RVs were tested by polymerase chain reaction (PCR). Bacteria were detected by urinary antigen, conventional culture and PCR.ResultsMean (SD) age and median (IQR) PSI score of 954 patients enrolled was 45.2 (19.5) years (range 14–94) and 42 (36). RVs were found in 262 patients (27.5%): influenza virus A (IFV A, 9.9%) comprised of pandemic H1N1 (6.7%) and seasonal H3N2 (3.5%), human rhinovirus (4.3%), adenovirus (4.2%), human metapneumovirus (1.8%), parainfluenza virus 1, 3 and 2 (1.7%, 1.5% and 1.2%). Influenza virus B, enterovirus, respiratory syncytial virus, human coronavirus and parainfluenza virus 4 were rarely detected (<1%). Frequency of IFV A was highest among patients aged between 45–64 years (p < 0.001), while adenovirus among patients aged 14–17 years (p < 0.001), no differences was found in other RVs. The proportion of pandemic H1N1 increased with severity of pneumonia evaluated by PSI (P < 0.05).ConclusionsThe proportion of RVs in CAP is higher than previously reported. IFV A pneumonia are usually found in patients older than 45 years, while, adenovirus pneumonia are common in adolescents and young adults. Pandemic H1N1 virus is still recognized by PSI as a high-severity pathogen. The findings contribute baseline data on viral CAP study in China.